This is interesting, given that the N-terminal Nlys residue in ADP3 was not critical for IgY binding, possibly suggesting that the screening hits bind in a different fashion to the antibodies than does ADP3.
In contrast, when the carboxylate moiety is in ortho, ligands like diclofenac or meclofenamic acid bind in a different orientation.
Finerty and Bass suggest, on the basis of the difference in affinity of the N-terminal and C-terminal zinc fingers of ZFa, that these regions of the protein may bind to different forms of dsRNA or alternatively may bind in a different manner.
Alternatively, l-serine may allosterically bind in a different location, causing the C-terminal Cys 458 to be released from the Fe S cluster and subsequently to bind to His 124 and Asn 126, which could serve as a latch to prevent it from interfering with subsequent substrate binding at the active site.
Further, when a regulatory motif is not palindromic (motifs in this study are not palindromic), the cognate protein is likely to bind in a different orientation (relative to the TSS) to, for example, a CACA motif on the coding strand, as compared to a CACA motif on the non-coding strand.
Topiramate, another sugar-based CA inhibitor, binds in a completely different manner to CA II as compared to the sulfonamide investigated here.
Celecoxib, a structurally related COX-2 inhibitor for which the X-ray crystal structure was reported earlier, binds in a completely different manner to hCA II as compared to valdecoxib.
Alternatively, the apparently detrimental effect of the oxidized nicotinamide group may be a false indication if the ADP-ribose molecule binds in a conformation different from that of the ADP-ribose moiety of a bound nucleotide.
Analysis of the impact of this asymmetry on actin and myosin interactions by sensitized emission luminescence resonance energy transfer spectroscopy and a unique fluorescent nanocircuit design reveals that the troponin affects the structure and function of myosin heads bound nearby in a different manner than myosin heads bound further away from the troponin.
